High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study.
BACKGROUND
To improve survival of elderly patients with primary central nervous system lymphoma (PCNSL), we conducted a phase II study with high-dose methotrexate (MTX) combined with procarbazine and CCNU. To reduce neurotoxicity, whole-brain irradiation was reserved for patients not responding to chemotherapy.


METHODS
High-dose MTX was applied on days 1, 15, and 30, procarbazine on days 1-10, and CCNU on day 1. Study treatment comprised up to three 45-day cycles. There was no lower limit of Karnofsky performance status (KPS).


RESULTS
Thirty patients with PCNSL (n = 29) or primary ocular lymphoma (n = 1) were included (median age 70 years, range 57-79 years). The median initial KPS was 60% (range 30%-90%). Best documented response in 27 assessable patients were 12 of 27 (44.4%) complete remissions, 7 of 27 (25.9%) partial remissions, and 8 of 27 (29.6%) disease progressions. Two patients died of probable treatment-related causes. With a median follow-up of 78 months (range 34-105), the 5-year overall survival is 33%. Eight of 30 patients (26.7%) are currently alive and well, six without signs of leukoencephalopathy.


CONCLUSIONS
The combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy. Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients.
Illerhaus
G
G
Department of Haematology, University Medical Center Freiburg, Freiburg, Germany.
Marks
R
R
Müller
F
F
Ihorst
G
G
Feuerhake
F
F
Deckert
M
M
Ostertag
C
C
Finke
J
J
D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D007970:Leukopenia / Q000139:chemically induced; D008130:Lomustine / Q000008:administration & dosage* / Q000627:therapeutic use; D008137:Longitudinal Studies; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D011344:Procarbazine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome
D011344:Procarbazine; D008130:Lomustine; D008727:Methotrexate